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标题：Contribution of Nitric Oxide to Potassium Bromate-Induced Elevation of Methaemoglobin Concentration in Mouse Blood
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作者：Satoshi Watanabe ; Shin-ichi Togashi ; Tetsuya Fukui 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2002
卷号：25
期号：10
页码：1315-1319
DOI：10.1248/bpb.25.1315
出版社：The Pharmaceutical Society of Japan
摘要：Bromate, an inorganic oxyhalide disinfection by-product, is known to cause kidney damage, haemolysis and methaemoglobinemia. In potassium bromate (KBrO₃)-treated mice (1.2 mmol/kg), elevation of methaemoglobin (MetHb) concentration in blood was observed simultaneously with an elevation of the NO concentration and attenuation of glutathione peroxidase (GPx) activity. Renal oxidative stress and kidney damage were also confirmed in the KBrO₃-treated mice. A pre-administered GPx-mimic ebselen (2-phenyl-1,2-benzisoselenazol-3(2 H )-one) dose-dependently diminished the KBrO₃-induced changes in MetHb concentration and GPx activity. Renal oxidative stress and kidney damage caused by the KBrO₃ administration were also dose-dependently suppressed by ebselen. On the other hand, ebselen did not suppress the KBrO₃-induced elevation of the NO concentration. KBrO₃-induced methaemoglobinemia, renal oxidative stress and kidney damage, consequently, seemed to result from the attenuation of GPx activity. Besides, the enhancement of NO production was not likely to be a result but a cause for the KBrO₃-induced attenuation of GPx activity. In in vitro experiments, oxidation of human oxy-haemoglobin (HbO₂) to MetHb was observed in a reaction mixture containing HbO₂ and an NO donor, NOC-7 (1-hydroxy-2-oxo-3-( N -methyl-3-aminopropyl)-3-methyl-1-triazene) or SIN-1 (3-(4-morpholinyl)sydnonimine), and this oxidation was inhibited by the NO scavenger carboxy-PTIO (2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide). However, no MetHb formation was observed in a reaction mixture containing HbO₂ and KBrO₃. These results suggest that KBrO₃-induced methaemoglobinemia results from the reduction of GPx activity in blood by the KBrO₃-induced increases in superoxide, NO and ONOO⁻.
关键词：potassium bromate;methaemoglobin;ebselen;nitric oxide;glutathione peroxidase